Photoredox Catalyzed Single C−F Bond Activation of Trifluoromethyl Ketones: A Solvent Controlled Divergent Access of gem ‐Difluoromethylene Containing Scaffolds
- Resource Type
- Authors
- Soumen Ghosh; Zheng‐Wang Qu; Sourav Roy; Stefan Grimme; Indranil Chatterjee
- Source
- Chemistry – A European Journal. 29
- Subject
- Organic Chemistry
General Chemistry
Catalysis
- Language
- ISSN
- 1521-3765
0947-6539
Selective defluorinative functionalization of trifluoromethyl ketones is a long-standing challenge owing to the exhaustive mode of the process. To meet the demands for the installation of the gem-difluoromethylene unit for the construction of the molecular architectures of well-known pharmaceuticals and agrochemicals, a distinct pathway is thereby highly desirable. Here, we introduce a protocol that allows the divergent synthesis of gem-difluoromethylene group containing tetrahydrofuran derivatives and linear ketones via single C-F bond activation of trifluoromethyl ketones using visible-light photoredox catalysis in the presence of suitable olefins as trapping partner. The choice of appropriate solvent and catalyst plays a significant role in controlling the divergent behavior of this protocol. Highly reducing photo-excited catalysts are found to be responsible for the generation of α,α-difluoromethyl ketone (DFMK) radicals as the key intermediate via a SET process. This protocol also results in a high diastereoselectivity towards the formation of partially fluorinated cyclic ketal derivatives with simultaneous construction of one C-C and two C-O bonds. State-of-the-art DFT calculations are performed to address the origin of diastereoselectivity as well as the divergence of this protocol.